During the critical week of embryonic cardiac septation, the initially tubular primitive heart loops and becomes divided into its 4 definitive chambers. This 5-year program of morphological and histochemical studies of embryonic chicks, rats and pigs will 1) extend a currently funded project entitled "Morphogenesis of Cardiac Outflow" (NHLBI R01-28936) and 2) develop and test new models of ventricular muscle fiber reorientation during the cardiac septation period. Over the past ten years, tissue associations and movements responsible for the morphogenesis of cardiac outflow structures have been described using a variety of morphological techniques. Mapping and marking experiments in the chick and correlative computer graphic reconstructions of hearts from rat and human embryos have described a structural septation complex which retracts and rotates as the semilunar valves and ventricular outflow tracts develop from the initially tubular conus cordis and trancus arteriosus. The specific aims of current activity are to: 1) map and illustrate relative movements of myocardial and conal cushion tissue below the semilunar valves; 2) characterize the ultrastructure and cytochemistry of mesenchymal condensations within the septation complex; 3) document patterns of DNA synthesis along the conal myocardial sleeve; and 4) follow changes in these parameters following teratogenic insult to chicks and rats. How myocardial fiber geometry develops in one of the most interesting and potentially fruitful of many questions raised by modeling of the outflow tract, since retraction and rotation of the semilunar valves is probably caused, or at least reflected, by a combination of differential cell growth and uneven functional stress within the conal or subjacent myocardium. Our starting model for divergence of the initially concentric fiber geometry toward the complex imbricated whorls present a week later suggests that the earliest ventricular trabeculae serve as "purse strings" to sense or sustain stress and conduct contractility in the looped tubular heart. The specific aims of the proposed fiber geometry studies are to 1) map and illustrate changes in muscle fiber orientation and cell proliferation in the subvalvular outflow tracts and ventricular wall during and immediately following the septation period; 2) map the appearance, distribution and 3-D orientation of atriopeptin rich ventricular muscle fibers, which we have recently described in the developing rat and 2) correlate these findings with comparative morphological studies of the developing pig heart. The proposed structural studies should lead to future studies of early cardiac function and function/structure relationships and further our long-range goal of describing cardiac morphogenesis during the septation period in detail sufficient to understand cardiac malformation.